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Purpose: To assess subretinal fibrosis (SF) occurrence in neovascular age-related macular degeneration (nAMD), according to macular neovascularisation (MNV) subtypes., Methods: A Retrospective national multi centre cohort study included eyes with naive nAMD. Main outcome measures were, according to MNV subtypes, cumulative incidence for SF, risk factors, and best corrected visual acuity (BCVA) for 36 months., Results: Four hundred and twenty eyes were included. Cumulative incidence of SF was 34.3% at 1 year, 39.0% at 2 years and 50.6% at 3 years. In multivariable analysis, Type 2 and mixed type 1 and 2 MNV were associated (p < 0.001) with a more frequent and rapid development of SF (respectively 85.5% and 81.0% at 1 year, then 95.8% and 93.1% at 3 years) than Types 1 and 3 (respectively 11.3% and 3.6% at 1 year, then 22.9% and 12.7% at 3 years). In Type 2 and mixed type 1 and 2 MNV combined, at baseline a worse BCVA (p = 0.02) and a higher maximal subretinal hyperreflective material (SHRM) thickness (p = 0.005) were associated with SF development at 3 years. In Type 1 MNV, the presence at baseline of intraretinal fluid (IRF) (p = 0.007) or SHRM (p < 0.001) and a higher percentage of visits with IRF (p < 0.001) or with SHRM (p < 0.001) were associated with SF occurrence. For Type 3 MNV, only a higher percentage of visits with SHRM (p = 0.001) was associated with SF. Including all MNV subtypes, eyes with a worse BCVA at baseline were associated with SF development (p < 0.001). Conversely, presence of SF at 3 years was associated with a worse baseline BCVA (p < 0.001)., Conclusion: Occurrence of SF differs when considering apart MNV subtypes., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD). Phase 3 trials demonstrated non-inferiority of anti-VEGF therapy with brolucizumab compared with aflibercept in best corrected visual acuity (BCVA) gains, with superior anatomical outcomes after brolucizumab. The purpose of the review was to summarize real-world efficacy and safety data on brolucizumab in patients with nAMD. The review protocol was registered with PROSPERO (ID: CRD42021290530). We conducted systematic searches in Embase, Medline and key ophthalmology congress websites (19 October 2021). Original reports of efficacy and/or safety in patients receiving brolucizumab to treat nAMD in clinical practice were eligible. The descriptive summary includes reports describing at least 10 brolucizumab-treated eyes. In total, 2907 brolucizumab-treated eyes from 26 studies were included. Outcomes were available for treatment-naive eyes (six studies), eyes switched to brolucizumab from other anti-VEGFs (16 studies), and/or treatment-naive and switch eyes combined (eight studies). Follow-up time points ranged from 4 weeks to 1 year post-brolucizumab initiation. For BCVA, significant improvements compared with brolucizumab initiation were reported in four of six studies in treatment-naive eyes (mean BCVA improvement, range: +3.7 to +11.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and in three of 12 studies in switch eyes (range: +9.0 to +15 ETDRS letters) (all p < 0.05); remaining studies reported no significant post-brolucizumab BCVA changes. For central subfield thickness (CST), improvements post-brolucizumab initiation were reported in all six studies in treatment-naive eyes (mean CST improvement, range: -113.4 to -150.1 μm) and in eight of 11 studies in switch eyes (range: -26 to -185.7 μm) (all p < 0.05). The 14 studies reporting on intraretinal, subretinal and/or total fluid observed improvements post-brolucizumab initiation. The four studies comparing treatment intervals observed extension of the interval between injections after switching to brolucizumab from other anti-VEGFs. Incidence of intraocular inflammation ranged from 0% to 19%. In conclusion, real-world efficacy and safety data concur with brolucizumab pivotal trials. Additionally, reduction of disease activity in anti-VEGF switch eyes was demonstrated by fluid reduction and/or visual acuity gain, along with prolongation of the interval between injections., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The aim of the present study was to determine whether microperimetric parameters could predict the progression of an eye at high risk of age-related macular degeneration (AMD) at 24 months., Methods: We conducted a multicentric prospective non-comparative open-label study including patients with one eye in stage 4 of the Age-Related Eye Disease Study Group (AREDS) classification, and the other eye in AREDS stage 3 (study eye). A microperimetry examination (MAIA™, CenterVue, Padova, Italy) was performed at baseline and every 6 months during the 2-year follow-up. At the end of the follow-up, each study eye was classified as 'progressive' (i.e. AREDS stage 4) or 'non-progressive' (i.e. AREDS stage 3)., Results: A total of 147 patients were analysed, of which 30.6% progressed from AREDS stage 3 to stage 4. The microperimetry criterion 'mean retinal sensitivity' was significantly different at baseline between non-progressive and progressive eyes (p = 0.022), with lower values for the latter. With a threshold for mean retinal sensitivity set at 24.7 dB, diagnostic sensitivity was 80% [95%CI (65.4-90.4)], specificity was 30.4% [95%CI (21.7-40.3)], positive predictive value was 33.6% [95%CI (24.8-43.4)], and negative predictive value was 77.5% [95%CI (61.5-89.2)]. In the multivariate analysis including microperimetric parameters and other routine ophthalmologic examinations, mean retinal sensitivity was the only predictive parameter statistically associated with progression (p = 0.0004)., Conclusions: Our findings are encouraging as regards the use of microperimetry, and mean retinal sensitivity value in particular, to predict the 2-year risk of progression to AREDS stage 4 eye., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate mean change in best-corrected visual acuity (BCVA) at 52 weeks in patients with inflammatory choroidal neovascularization (CNV) treated with aflibercept., Methods: We conducted a prospective non-comparative open-label trial. Following one mandatory intravitreal injection of aflibercept, patients were treated under a pro re nata (PRN) dosing regimen with monthly visits., Results: A total of 19 patients were included, but one presented exclusion criteria; 16 patients were followed for the whole 52-week study, and data for the primary endpoint analysis were available for 14. At baseline, mean BCVA and mean central retinal thickness (CRT) were 64.53 (±19.64) letters and 351.79 (±97.77) μm, respectively. At 52 weeks, the mean change in BCVA was +9.50 (±12.90) letters [95%CI = +2.05-+16.95]. One patient had lost more than 15-letters at 24 weeks, and another one at 52 weeks. CRT change was -62.77 (±100.73) μm at 24 weeks and -66.53 (±97.47) μm at 52 weeks. There was a mean number of 3.56 (±3.29) intravitreal injections at 52 weeks (min = 1; max = 12). No serious ocular adverse events related to the treatment were reported., Conclusions: Our study shows that aflibercept is clinically effective, both anatomically and functionally in the treatment of inflammatory CNV. Following the first injection, the PRN strategy appears sufficient for treating most choroidal neovessels., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The aim of this study was to evaluate the impact of adherence to French coronavirus disease 2019 (COVID 19)-related guidelines for intravitreal injection (IVI) practice on the visual outcomes of patients treated with anti-vascular endothelial growth factor (VEGF) agents for macular diseases during the first lockdown period., Methods: Observational multicentre study including all patients from 18 centres with an IVI initially planned during the lockdown. Visual acuity (VA, ETDRS) was recorded at 1 and 4 months after lockdown. French COVID 19-related guidelines recommended maintaining IVI practice. We defined three groups of patients: A, adherent to guidelines; NA+, non-adherent with delayed IVIs; and NA-, non-adherent without IVIs performed during the lockdown. Risk factors for non-adherence and visual loss were studied., Results: A total of 3020 eyes of 3020 patients, aged 77.8 ± 11.6 years, 59.8% women, were included. 59.3% were non-adherent(46.7% NA+, 12.6% NA-). A smaller decrease in VA at 4 months was observed in the A group than the NA+ and NA- group (-0.2 ± 6.7, -0.3 ± 6.9 and -1.5 ± 6.9, respectively [p < 0.001]). Factors associated with non-adherence were in multivariable analysis, older age, hospital practice, low-density population areas, high viral incidence areas, longer intervals between injection and treat and extent protocol. Factors associated with visual loss at 4 months in multivariable analysis were, being in the NA- group, older age, T&E and fixed regimens., Conclusion: Strict adherence to guidelines was associated with better visual outcome, although most of our patients did not attend as planned. Identification of patients at risk could help in the future in case of a new pandemic lockdown., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The aim of this systematic literature review was to describe patient-reported outcomes, mental health and caregiver burden in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents in routine clinical practice., Methods: Electronic searches were conducted in Embase and MEDLINE according to pre-defined criteria., Results: Of 856 records identified, 63 met inclusion criteria. Depression or depressive symptoms were reported in up to 42% of patients with nAMD. Of 25/63 (40%) studies evaluating quality of life (QoL) and using various tools, eight studies reported composite National Eye Institute Visual Functioning Questionnaire scores following anti-VEGF treatment. Of these, seven reported a statistically significant improvement at the earliest time point measured (Month 3-12) and approximately 50% reported sustained QoL benefits at 12 months. In studies comparing the attributed or different regimens, the most important factor from the patient's perspective was the likelihood that a particular regimen would maintain vision. There was a preference towards treat and extend, which was associated with a perceived reduction in patient and caregiver burden, compared to fixed dosing., Conclusions: A coordinated holistic approach to patient care is key to optimizing patient well-being as well as visual outcomes. Further research regarding the patient-reported impact of nAMD management outside the trial setting (particularly international longitudinal studies) is warranted. Standardization of QoL studies would assist in establishing whether sustained QoL improvement, rather than prevention of QoL decline, should be a realistic expectation of treatment of nAMD in the longer term., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To assess the impact of intravitreal injections (IVTI) on ocular surface of patients treated with multiple injections., Methods: Prospective, tricentric study conducted in patients treated with unilateral IVTI. An asepsis protocol with povidone-iodine was used for all patients during IVTI. The primary endpoint was the difference between the pre-IVTI Ocular Surface Disease Index (OSDI 1) score and that measured on day one (D1) post-IVTI (OSDI 2). Secondary endpoints were the evaluation of predictive factors for OSDI scores, pain assessment on D1, and the Lacrydiag® analysis of tears from the injected eye versus contralateral eye before IVTI., Results: Two hundred and nineteen patients with a mean age of 75.9 ± 10 years were included. The mean OSDI2-OSDI1 difference was 19.2 ± 20.6 (p < 0.001). The mean noninvasive tear break-up time was 6.41 ± 4.59 seconds in the injected eye versus 7.36 ± 4.36 seconds in the contralateral eye (p < 0.001). In the multivariate analysis, the factors significantly associated with the OSDI 2 score were the OSDI 1 score (p < 0.001), the pain score on D1 (p < 0.001) the number of instilled glaucoma eye drop (p = 0.01) and a centre effect (centres 2 and 3 versus centre 1, p < 0.001)., Conclusion: Our results confirm the impairment of the ocular surface and quality of life immediately after an IVTI. These results suggest 3 levels of action to improve the immediate tolerance: improving the basal status of the ocular surface, reducing the contact time with povidone-iodine that might be toxic to the surface, and improving immediate post-IVTI treatment., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Numerous small hyperreflective dots (HRDs) can be seen within the hyporeflective layer between the ellipsoid zone (EZ) and the interdigitation zone (IZ) on C-scan spectral-domain optical coherence tomography (SD-OCT) with a yet unknown variation under light conditions. The aim of this study was to explore light-induced SD-OCT changes in these HRDs., Methods: The study subjects were randomly assigned to two groups: Group 1 experienced a dark adaptation protocol followed by intense retinal photobleaching, while Group 2, serving as the control group, was exposed to constant ambient light without any variation. The number of HRDs was automatically counted., Results: Twenty healthy volunteers were prospectively included. The number of HRDs differed significantly over time (p = 0.0013). They decreased in Group 1 after dark adaptation and retinal photobleaching before returning to baseline levels 30 min later; conversely, they remained relatively constant in Group 2 throughout the study (p < 0.001). Light-skinned subjects had less HRD than dark-skinned subjects., Conclusion: We observed light-induced modifications in the space between the EZ and the IZ. We hypothesize that the HRDs visible in this zone correspond to melanosomes that are mobilized during the light stimulation protocol. Larger studies are recommended to further evaluate and confirm light-induced SD-OCT changes under physiological and pathological conditions., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10., (© 2021 Wiley Periodicals LLC.)

Purpose: The aim of this study was to determine whether choroidal thickness (CT) increases at the time of exudative recurrence in diabetic patients with unilateral diabetic macular oedema (DME) treated with intravitreal injections of anti-VEGF or dexamethasone., Methods: A real-life, prospective, two-centre study was conducted over a 9-month period investigating diabetic patients presenting with unilateral DME treated with anti-VEGF or dexamethasone intravitreal injections, and CT was measured manually, using the enhanced depth imaging module of the spectral domain optical coherence tomography. Choroidal thickness (CT) was measured in the morning, in both the affected and healthy eye of each patient at two timepoints: when the macula was 'dry' (T0) and at the time of exudative recurrence (T1)., Results: A total of 51 patients with unilateral DME were included. Mean CT in the affected eye was significantly thicker at the time of exudative recurrence (210.8 ± 44.1 μm at T0 versus 238.0 ± 49.0 μm at T1, p < 0.001). There was no significant variation in CT in the fellow eye (214.4 ± 52.3 µm at T0 versus 218.9 ± 53.4 µm at T1, p = 0.53). The type of intravitreal injection, the number of injections and the CT at T0 had no influence on the change in CT., Conclusion: This study found that CT increased significantly in the affected eye at the time of recurrence of DME treated with anti-VEGF or dexamethasone injections. Choroidal thickness (CT) could constitute an interesting new indicator for monitoring patients with DME., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To develop a risk-prediction nomogram based on baseline variables for good functional response during the 1st year of treatment with anti-VEGF agents in naive diabetic macular oedema (DME)., Methods: This retrospective study included patients presenting naive-DME treated with anti-VEGF therapy at Dijon University Hospital (France) between 1 February 2012 and 31 March 2015 (derivation cohort). We studied baseline variables that had significant associations with a good functional response to anti-VEGF agents during the 1st year of treatment. We used a program to generate a nomogram based on a binary logistic regression predictive model. Then, this nomogram was tested on data from a separate cohort of naive-DME patients from a multicenter study involving 20 French ophthalmologic centres between January 2014 and June 2015 (validation cohort)., Results: Age, baseline BCVA and ellipsoid zone integrity on spectral-domain optical coherence tomography (SD-OCT) are functional prognostic factors and were used to build a nomogram. The nomogram showed excellent discrimination for good functional responders (area under the curve (AUC) = 0.906, 95% confidence interval (95% CI) = [0.849-0.964], p = 0.004). The discriminative power of this nomogram was tested on the validation cohort data, demonstrating good discrimination of good functional responders (AUC = 0.942, 95% CI = [0.898-0.986], p < 0.001)., Conclusion: This nomogram provides a useful estimation of a good functional response in naive-DME patients treated with anti-VEGF agents., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare the risk of haemorrhagic complications in elective macular surgery between patients with no antithrombotic (AT) treatment (defined as patients with no history of AT therapy or who discontinued AT therapy) and patients who continued AT treatment during the surgery., Methods: E-case report forms were prospectively recorded in a database before vitreoretinal surgery and 1 month after. Data on patient characteristics, surgical techniques, haemorrhagic complications and antithrombotic status were collected. Patients with retinal detachment, proliferative diabetic retinopathy and previous retinal haemorrhage were excluded., Results: A total of 748 procedures (single procedure in one eye per patient) were performed between January and May 2019. Among them, 202 patients (27.0%) were treated with antithrombotic therapy at the time of surgery: 19.5% with antiplatelet agents (n = 146), 6.3% with anticoagulants (n = 47) including 3.2% (n = 24) patients treated with novel oral anticoagulants, 0.8% (n = 6) with anticoagulants and antiplatelet agents, and 0.4% (n = 3) with heparin. Overall, 92 patients (12.3%) developed one or more haemorrhagic complications, of which 63 (11.5%) and 29 (14.4%) were in the non-AT and AT group, respectively. The multivariate logistic regression model showed no difference between AT treatment groups regarding ocular bleeding complications (odds ratio [OR] 1.2, 95% confidence interval (CI) [0.7-2.2], p = 0.54)., Conclusion: No cases of uncontrolled or severe perioperative haemorrhage in patients continuing antithrombotic agents were reported in this selected population. For the majority of the patients taking antiplatelets or anticoagulants, these agents could be safely continued during macular surgery., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The use of planar ultra-widefield fundus photography (UWF) may result in distortions and inaccurate measurement. The aim of the study was to evaluate the accuracy of UWF instead of the standard narrow field (SF) for the treatment planning phase of ocular tumours., Methods: Distortions between conformal SF and UWF were assessed in 43 patients with choroidal melanoma treated with either proton therapy or brachytherapy. imagej software was used to measure distortion., Results: The median interquartile range ([IQR]) distortion for all cases was 3.7% [1.7-10.8]. For cases with tumours within 6 mm of the optic disc, distortions appeared clinically nonsignificant. For peripheral and/or large tumours, significantly larger distortions were observed on UWF (median 4.4% [2.7-22.6] for tumours ≥6 mm from the optic disc versus 3.3% [1.6-9.9] for those <6 mm, p = 0.04). Images can be subdivided into three groups: minimal distortion (79.1% of eyes), similar level of major distortion for both measured distances (11.6%) and distortion with unequal level of distortion between the measured distances (9.3%)., Conclusion: Distortions with UWF appeared minimal in posterior regions of the fundus and increased with the distance from the posterior pole. UWF could therefore be used for treatment planning of ocular tumours as the planned radiation dose to the macula and optic disc are not impacted., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare central retinal thickness (CRT) after panretinal photocoagulation (PRP) with a multispot semi-automated PAttern-SCAnning Laser (PASCAL) in one session (SS-PRP) versus four monthly sessions (MS-PRP) in diabetic retinopathy., Methods: Multicentre, prospective, randomized, single-blinded, controlled trial evaluating the noninferiority of SS-PRP versus MS-PRP for CRT measured with macular spectral-domain optical coherence tomography (SD-OCT), with a 9-month follow-up in patients presenting severe nonproliferative diabetic retinopathy (DR) or mild proliferative DR without macular oedema (ME) at baseline., Results: Ninety-seven eyes of 97 participants with a mean age of 57.0 ± 14.2 years were included. The mean change of CRT from baseline to 9 months was not statistically different in SS-PRP or in MS-PRP: +16.9 ± 28.3 μm versus +24.7 ± 31.8 μm, respectively (p = 0.224). The variation in mean best-corrected visual acuity (BCVA) from baseline to 9 months was similar in both groups: -1.1 ± 6.5 letters versus -0.6 ± 6.2 letters (p = 0.684). The number of patients with stabilization of DR was not statistically different between the two groups. No severe complication was recorded in either group., Conclusion: This study showed the noninferiority of PRP performed in one session versus four monthly sessions with a PASCAL concerning central retinal thickness for treating mild proliferative or severe nonproliferative DR without ME at baseline., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings., Methods: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency., Results: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3-5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) μm, and the mean change in CRT was -115.2 μm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters)., Conclusion: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring., (© 2018 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Orthodenticle homeobox 2 (OTX2) controls essential, homeostatic retinal pigment epithelial (RPE) genes in the adult. Using cocultures of human CD14 + blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human-induced pluripotent stem cell-derived RPE cells, we show that activated Mos markedly inhibit RPEOTX2 expression and resist elimination in contact with the immunosuppressive RPE. Mechanistically, we demonstrate that TNF-α, secreted from activated Mos, mediates the downregulation of OTX2 and essential RPE genes of the visual cycle among others. Our data show how subretinal, chronic inflammation and in particular TNF-α can affect RPE function, which might contribute to the visual dysfunctions in diseases such as age-related macular degeneration (AMD) where subretinal macrophages are observed. Our findings provide important mechanistic insights into the regulation of OTX2 under inflammatory conditions. Therapeutic restoration of OTX2 expression might help revive RPE and visual function in retinal diseases such as AMD., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Purpose: To compare the anti-adhesive effect of cefuroxime and moxifloxacin on the primary attachment phase of Staphylococcus epidermidis on hydrophobic acrylic intraocular lenses (IOLs)., Methods: Forty hydrophobic acrylic IOLs were used. Two groups of IOLs were soaked in a moxifloxacin (Mox-T1: 0.5 mg/0.1 ml) or a cefuroxime (Cef-T1: cefuroxime 1 mg/0.1 ml) solution before incubation in a S. epidermidis bacterial suspension. Two other groups were incubated in the bacterial suspension before antibiotics (Cef-T2 and Mox-T2) were added. The control group (Ctrl) consisted of IOLs incubated in the bacterial suspension. After incubation, IOLs were sonicated and vortexed. The resultant suspension was spread over a nutritive agar plate. Bacterial colonies were counted after 24 hr of incubation., Results: Mean number of colony-forming units per IOL was Cef-T1: 184 × 10(3) (SE: 5.24; SD: 28.21), Cef-T2: 117 × 10(3) (SE: 5.74; SD: 30.37), Mox-T1: 1.27 × 10(3) (SE: 0.12; SD: 0.61), Mox-T2: 25 × 10(3) (SE:1.98; SD: 9.72) and Ctrl: 361 × 10(3) (SE: 26.9; SD: 107.6). The number of adhering bacteria did not vary whether cefuroxime was added before or after IOL incubation in the bacterial suspension (p = 0.132). Moxifloxacin was more effective in reducing the number of adhering bacteria when used before IOL incubation (p < 0.001). Overall for T1 and T2, moxifloxacin was more effective than cefuroxime in reducing bacterial adhesion on IOLs (p < 0.001)., Conclusion: Moxifloxacin and cefuroxime significantly reduced S. epidermidis adhesion on hydrophobic acrylic IOLs. The anti-adhesive effect was superior with moxifloxacin., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Small choroidal melanomas have a better prognosis than large tumours. However, these small tumours can spread, often late in their course. The aim of the study was to analyse survival and tumour characteristics of six cases of late metastatic diseases after conservative treatment., Methods: A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon among 523 patients treated between 1991 and 2010 by proton beam therapy (508) or brachytherapy with 106 (Ru/Rh) (15) for uveal melanomas. We have selected patients with small choroidal melanoma (thickness≤3 mm and diameter≤9 mm) (59 patients), who have developed hepatic metastases (six of 59)., Results: At the time of diagnosis, median age was 57 years (range, 37-82 years). The mean tumour thickness was 2.9 mm (range 2.5-3 mm), and the mean diameter was 7 mm (5-8 mm). Orange pigment was observed in four cases, subretinal fluid was observed in two cases, and one tumour touched the optic disc. Five patients had proton beam therapy. One patient had beta brachytherapy (106 Ru/106 Rh). Average follow-up was 8.3 years (range 4.2-11.8 years). None of the six patients developed local tumour recurrence. The mean survival time after diagnosis of melanoma was 9.8 years (range, 4.9-14.6 years). The average time from treatment of primary tumour to detection of liver metastasis was 7 years (range 3.9-12 years). The mean survival time from the diagnosis of metastasis was 35.2 months (range 9-101 months). Small melanoma-related death was 0% at 3 years, 1.7% at 5 years, 5.1% at 10 years and 10.2% at 15 years in our series., Conclusions: Despite a small tumoral size and an early and effective local treatment, six of 59 small choroidal melanomas have developed metastasis after local treatment. Small tumours represent a significant risk of metastasis., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the efficacy and the safety of uveal melanoma transretinal biopsy using 25-gauge vitrectomy system., Methods: At the patient's request of a tissue diagnosis, nine posterior uveal melanomas treated by proton-beam therapy were biopsied during the insertion of tantalium markers., Results: The diagnosis was uveal melanoma, confirmed in all cases using cytological (7 of 9) and histological analysis (2 of 9). Immunocytochemistry was performed on all samples (9 of 9). In eight of nine patients, minor postoperative vitreous haemorrhages were seen, which resolved in 1 day. No other ocular complications were noticed., Conclusion: Uveal melanoma biopsy using 25-gauge vitrectomy system is a valuable procedure to confirm the diagnosis, with adequate sample and low ocular morbidity., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To determine whether indomethacin 0.1% eye drops are at least as effective as ketorolac 0.5% eye drops in treating ocular inflammation following cataract surgery., Methods: Prospective, multicenter, investigator-masked, parallel-group, randomized, active-controlled clinical trial. Cataract patients were randomized in a 1:1 ratio to receive indomethacin or ketorolac administered QID for 3 weeks beginning 1 day before surgery. The primary end-point was aqueous flare measured by laser flare meter at postoperative Days 1 and 7. Secondary end-points included retinal thickness, slit lamp and funduscopic examinations and postsurgical pain ratings. Safety and tolerability were also assessed., Results: A total of 86 patients were included in the per protocol population (n = 43 per treatment group). Indomethacin was found non-inferior to ketorolac for comparison of aqueous flare at postoperative Days 1 and 7 (Day 1: 95% CI: -2.37, 5.50; non-inferiority upper margin, 15 ph/ms and Day 7: 95% CI: -7.83, -0.94; non-inferiority upper margin, 8 ph/ms) and statistically better than ketorolac at Day 7 (p = 0.013). There were no significant between-group differences in aqueous flare and change from baseline in retinal thickness at postoperative Days 30 and 90. Indomethacin showed a higher subjective tolerance rating than ketorolac at postoperative Days 7 and 30 (p ≤ 0.044)., Conclusion: Indomethacin 0.1% was at least as effective as ketorolac 0.5% at Day 1 and more effective than ketorolac 0.5% at Day 7 in treating ocular inflammation after uncomplicated cataract surgery. Indomethacin was better tolerated than ketorolac. There were no clinically meaningful safety concerns with either treatment., (© 2012 Bosch and Lomb. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

We wished to assess whether ocular toxoplasmosis can be reactivated during pregnancy in immunocompetent females, and whether such reactivation is confined to the eye or whether the fetus is exposed to the risk of vertical transmission. For this purpose, we retrospectively examined 18 females with ocular toxoplasmosis during the course of 35 pregnancies. Of these 18 patients, seven developed recurrences during seven pregnancies. Due to the potential risk of functional damage to the mother and the possibility of vertical disease transmission to the fetus, we suggest following such cases carefully during pregnancy until the dimensions of the problem are more fully appreciated.